title: Cell lineage dynamics in the process leading to intestinal metaplasia.
abstract: BACKGROUND
  Gene expression in the early stage of the transition to intestinal metaplasia in human gastric mucosa has not been determined. In this study, we investigated the temporal relationship between cell lineage changes and intestine-specific gene expression in the process leading to intestinal metaplasia, using Cdx2-transgenic mice.
  
  
  METHODS
  Cellular phenotypes were analyzed by immunohistochemistry and were compared with the gene expression profiles of cell lineage markers by real-time polymerase chain reaction.
  
  
  RESULTS
  Up to postnatal day (PD) 20, the gastric mucosae of Cdx2-transgenic mice were histologically similar to those of their normal littermates. However, at approximately PD 20, we observed the sporadic appearance of glands in which all the epithelial cells expressed Cdx2 (Cdx2-diffuse positive glands). In the Cdx2-diffuse positive glands, parietal cells had disappeared, the proliferating zone had moved from the isthmus to the base, and absorptive cells and goblet cells were recognized. In contrast, the surrounding mucosa retained the phenotype of the gastric gland in which only some of the epithelial cells expressed Cdx2. During PDs 30 and 40, the entire fundic mucosa changed to transdifferentiated mucosa that was a composite of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia. An increase in the expression of intestine-specific genes, with a reciprocal decrease in gastric-specific gene expression, began much earlier than the emergence of Cdx2-diffuse positive glands.
  
  
  CONCLUSIONS
  A dramatic increase in intestine-specific gene expression precedes the morphological appearance of intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. 94036hs@jichi.ac.jp
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mutoh
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Miho
authors.initials: M
authors.lastname: Sashikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sugano
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D019070:Cell Lineage / Q000235:genetics*; D054338:Cell Transdifferentiation; D005753:Gastric Mucosa / Q000473:pathology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology*; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D015534:Trans-Activators